Use of sunscreen combinations comprising, as essential constituent, 4,4xe2x80x2-diarylbutadienes as photostable UV filters in cosmetic and pharmaceutical preparations
The invention relates to the use of sunscreen combinations which comprise, as constituent which absorbs in the UV-A region, 4,4xe2x80x2-diarylbutadienes, and at least one further sunscreen which absorbs in the UV-A region, UV-B region or in both regions, chosen from a group defined in detail below as photostable UV filter combination in cosmetic and pharmaceutical preparations for protecting the human epidermis or human hair against UV radiation, specifically in the range from 320 to 400 nm.
The sunscreens employed in cosmetic and pharmaceutical preparations have the task of preventing, or at least diminishing the consequences of, harmful effects of sunlight on the human skin. However, these sunscreens also serve to protect other ingredients from decomposition or degradation by UV radiation. In hair cosmetic formulations the aim is to reduce damage to the keratin fibers by UV rays.
The sunlight reaching the surface of the earth contains proportions of UV-B radiation (280 to 320 nm) and UV-A radiation ( greater than 320 nm), which are directly adjacent to the visible light region. The effect on the human skin is manifested, particularly in the case of UV-B radiation, by sunburn. Accordingly, the industry offers a relatively large number of substances which absorb UV-B radiation and thus prevent sunburn.
Dermatological investigations have now shown that UV-A radiation is also perfectly capable of causing skin damage and allergies by, for example, damaging the keratin or elastin. This reduces the elasticity and water storage capacity of the skin, i.e. the skin becomes less supple and tends to form wrinkles. The noticeably high incidence of skin cancer in regions where the sun""s radiation is strong shows that damage to the genetic information in the cells is evidently also caused by sunlight, specifically by UV-A radiation. All these findings would therefore suggest the need to develop efficient filter substances for the UV-A region.
There is a growing demand for sunscreens for cosmetic and pharmaceutical preparations which can be used in particular as UV-A filters and whose absorption maxima ought therefore to be in the range from about 320 to 380 nm. In order to achieve the required effect using the minimum amount, sunscreens of this type ought additionally to have a high specific absorbance. Sunscreens for cosmetic products must also meet a large number of other requirements, for example good solubility in cosmetic oils, high stability of the emulsions produced with them, toxicological acceptability, and low intrinsic odor and low intrinsic color.
Another requirement which sunscreens must meet is adequate photostability. However, this is only inadequately ensured, if at all, with the UV-A-absorbing sunscreens hitherto available.
French Patent No. 2 440 933 describes 4-(1,1-dimethylethyl)-4xe2x80x2-methoxydibenzoylmethane as a UV-A filter. It is proposed to combine this specific UV-A filter, which is sold by GIVAUDAN under the name xe2x80x9cPARSOL 1789xe2x80x9d, with various UV-B filters in order to absorb all UV rays having a wavelength from 280 to 380 nm.
However, this UV-A filter does not have sufficient photochemical stability, when used alone or in combination with UV-B filters, to ensure sustained protection of the skin during sunbathing for prolonged periods, which means that repeated applications at regular and short intervals are required if effective protection of the skin from all UV rays is desired.
For this reason, EP-A-0 514 491 discloses the stabilization of the insufficiently photostable UV-A filters by adding 2-cyano-3,3-diphenylacrylic esters which themselves act as filters in the UV-B region.
It has furthermore already been proposed in EP-A-0 251 398 and EP-A-0 416 837 to combine chromophores absorbing UV-A radiation and UV-B radiation into one molecule using a linker. This has the disadvantage that firstly a free combination of UV-A and UV-B filters in the cosmetic preparation is no longer possible, and that difficulties in the chemical linkage of the chromophores allow only certain combinations.
It is an object of the present invention to propose sunscreens for cosmetic and pharmaceutical purposes which absorb in the UV-A region with high absorbance, which are photostable, have low intrinsic color, i.e. a sharp band structure, and are soluble in oil or water depending on the substituent.
We have found that this object can be achieved advantageously by certain sunscreen combinations.
Accordingly, this object is achieved according to the invention by the use of sunscreen combinations comprising
A) compounds absorbing essentially in the UV-A region and
B) further compounds absorbing in the UV-A region, in the UV-B region and over both regions,
where the constituents absorbing in the UV-A region comprise effective amounts of at least
A) one 4,4xe2x80x2-diarylbutadiene of the formula I 
in which
R1 and R2 independently of one another are hydrogen,
C1xe2x80x94C20-alkyl, C3xe2x80x94C10-cycloalkyl or C3xe2x80x94C1O-cycloalkenyl,
and the constituents
B) comprise an effective amount of at least one compound chosen from the group consisting of
Ba) dibenzoylmethane compounds of the formula III 
in which
R3 is C1xe2x80x94C2-alkyl and
R4 is hydrogen, C1xe2x80x94C12-alkyl or C1xe2x80x94C12-alkoxy,
Bb) triazine derivatives of the formula IV 
in which
R5 to R7 independently of one another are optionally substituted C1xe2x80x94C20-alkyl, C5xe2x80x94C10-aryl, C5xe2x80x94C10-heteroaryl or SpSil, where Sp is a spacer and Sil is a silane, oligosiloxane or polysiloxane radical,
X is the divalent radical 
where
R8 is hydrogen or optionally substituted C1xe2x80x94C20-alkyl,
C5xe2x80x94C10-aryl or C5xe2x80x94C10-heteroaryl,
Bc) the triazine derivative of the formula V 
in which at least one o-hydroxyl group and at least one p-alkoxy group having 1 to 20 carbon atoms are bonded to the phenyl rings,
Bd) the benzotriazole derivative of the formula VI 
Be) the benzimidazole derivative of the formula VII 
Bf) the benzotriazole derivative of the formula VIII 
Bg) o,oxe2x80x2,p,pxe2x80x2-tetrahydroxybenzophenone of the formula IX 
Bh) an organosiloxane benzalmalonate of the formula Xa 
in which
V1 is the group 
V1 is a methyl group or V1xe2x80x2, or of the formula Xb 
in which V2is the group of the structure 
V2 is a methyl group or V2xe2x80x2
or mixtures of compounds of the formulae Xa and Xb,
where t is a value up to 100 and u is a value up to 20, with the proviso that u=0 when V1=V1xe2x80x2 and/or V2=V2xe2x80x2, and u is a value from 1 to 20 when V1=CH3 and/or V2=CH3,
as photostable UV filters in cosmetic and pharmaceutical preparations for protecting human skin or human hair against solar rays, optionally together with further compounds which absorb in the UV region and which are known per se for cosmetic and pharmaceutical preparations.
The sunscreen combination of the compounds (A) and (B) can be used alone or in combination with other compounds which absorb in the UV range, although at least effective amounts of the compounds (A) and (B) should be present in the sunscreen preparations. xe2x80x9cEffective amounts of the compounds (A) and (B)xe2x80x9d means generally in each case at least 0.2% by weight, in each case based on the cosmetic preparation.
In the sunscreen combinations according to the invention, the amount of compounds which absorb in the UV-S region usually predominates. Accordingly, the content of the compound (A) which absorbs in the UV-A range is generally 5 to 50% by weight, preferably 10 to 25% by weight, in each case based on sunscreen combination of (A) and (B).
The combinations of sunscreens (A) and (B) according to the invention have synergistic effects in sun protection action inasmuch as the protective action of the combinations exceeds the sum of the action of the constituents.
The compounds (A), i.e. 4,4xe2x80x2-diarylbutadienes of the formula I 
are known from EPA 916 335. The substituents R1 and/or R2 are preferably C1xe2x80x94C8-alkyl and C5xe2x80x94C8-cycloalkyl and very particularly neopentyl.
The compounds (B) are all known and are characterized below in more detail:
(Ba)
The compounds of the formula III are known from FR 2440933. A suitable and preferred compound of the formula III is p-methoxy-pxe2x80x2-t-butyl-dibenzoylmethane (R3=methoxy, R4=t-butyl).
(Bb)
Compounds of the formula IV where R5 to R7 are alkyl, aryl or heteroaryl are known from EP-A 0796851, EP-A 0087098 and EP-A 0850935. Suitable alkyl radicals are, in particular, straight-chain or branched C1 to C12 radicals, in particular C1 to C8 radicals. Aryl radicals are, for example, phenyl or naphthyl radicals, in particular phenyl radicals. Suitable heteroaryl radicals are single or fused ring systems having one or more heteroaromatic 3- to 6-membered rings. As heteroatoms, one or more nitrogen, sulfur and/or oxygen atoms may be present in the ring or ring system.
Compounds of the formula IV with the meaning SpSil are known from EPA 0 933 376.
The term spacer for Sp means in this connection a bivalent branched or unbranched C3xe2x80x94C12-alkylene chain or alkenylene chain which links the silane, oligosiloxane or polysiloxane moiety to the triazine radical.
Examples of a C3xe2x80x94C12-alkylene chain are propylene, 2-methylpropylene, butylene, pentylene and hexylene.
Examples of a C3xe2x80x94C12-alkenylene chain are 2-propen-2-ylene, 2-methyl-3-propenylene, 3-buten-3-ylene and 4-penten-4-ylene.
Preferred spacers are xe2x80x94(CH2)3xe2x80x94, xe2x80x94(CH2)4xe2x80x94, xe2x80x94(CH2)5xe2x80x94, xe2x80x94[CH(CH3)]xe2x80x94(CH2)xe2x80x94, xe2x80x94(CH2)2xe2x80x94CH=CHxe2x80x94, xe2x80x94C(=CH2)xe2x80x94CH2xe2x80x94, xe2x80x94C(=CH2)xe2x80x94(CH2)2xe2x80x94Oxe2x80x94(CH2)4xe2x80x94, xe2x80x94(CH2)4xe2x80x94Oxe2x80x94(CH2)2xe2x80x94.
The term silanes in this connection stands for a radical SiR9R10R11, in which R9, R10 and R11, independently of one another, are C1xe2x80x94C6-alkyl, C1xe2x80x94C6-alkoxy or phenyl.
Examples which may be mentioned are: Si(CH2xe2x80x94CH3)3, Si(CH2xe2x80x94CH2xe2x80x94CH3)3, Si(isopropyl)3, Si(tert-butyl)3, Si(tert-butyl)(CH3)2, Si(CH3)2 (hexyl), Si(OCH3)3, Si(OEt)3, SiPh3.
The term oligosiloxanes means a radical from the group of the general formula, consisting of SiR12m(OSiR123)n where m=0, 1 or 2; n=3, 2 or 1 and m+n=3, R12xe2x80x94[Si(R12)2xe2x80x94Oxe2x80x94]rxe2x80x94Si(R12)2xe2x80x94A and R12xe2x80x94[Si(R12)2xe2x80x94Oxe2x80x94]rxe2x80x94Si(A) (R12)xe2x80x94Oxe2x80x94Si(R12)3, in which A is a chemical bond or a spacer and R12 is a C1xe2x80x94C6-alkyl radical or phenyl radical, and r is a value from 1 to 9.
The term polysiloxane includes, for example, a radical from the group of the general formula, consisting of
A-[Si(R13)2xe2x80x94O]sxe2x80x94Si(R13)2xe2x80x94A or
(R13)3xe2x80x94Si[Oxe2x80x94Si(R13)2]]txe2x80x94[Oxe2x80x94Si(R13)(A)]qxe2x80x94Oxe2x80x94Si(R13)3, in which A is a chemical bond or a spacer and R16 is a C1xe2x80x94C6xe2x80x94alkyl radical or phenyl radical, s and t are values from 4 to 250 and q is a value from 1 to 30.
Suitable compounds of the formula IV are preferably the triazine compounds of the formula IVa 
or of the formula IVb 
(Bc)
Triphenyltriazines of the formula V substituted by at least one o-hydroxyl group and at least one p-alkoxy group are known from WO 99/66896.
In particular, triphenyltriazines of the formula Va are suitable 
in which X is hydrogen or a hydroxyl group and Y is a hydroxyl group,
R14 is hydrogen or alkoxy having 1 to 12 carbon atoms and
R15 and R16 are alkoxy having 1 to 12 carbon atoms.
Particular preference is given to the compound of the formula Vb 
(Bd)
The compound of the formula VI has the CAS No. 103597-45-1.
(Be)
The compound of the formula VII has the CAS No. 180898-37-7.
(Bf)
The compound of the formula VIII has the CAS No. 155633-54-8.
(Bg)
The compound of the formula IX has the CAS No. 131-55-5.
(Bh)
The compounds of the formulae Xa and Xb are known from EP-A 0920859.
Of the compounds of the formulae Xa and/or Xb those with the CAS numbers 208391-15-5, 208391-15-5D, 177955-90-7, 177955-90-7D and 177995-90-7DP are particularly suitable.
In the sunscreen combinations to be used according to the invention, it is possible for not only individual compounds (Ba) to (Bh) to be present, but also mixtures of two or more of these compounds.
The present invention further relates to cosmetic and pharmaceutical preparations which have 0.1 to 10% by weight, preferably 1 to 7% by weight, based on the total amount of cosmetic and pharmaceutical preparation, of a sunscreen combination comprising
A) compounds absorbing essentially in the UV-A region and
B) further compounds absorbing in the UV-A region, in the UV-B region and over both regions,
where the constituents absorbing in the UV-A region comprise effective amounts of at least
A) one 4,4xe2x80x2-diarylbutadiene of the formula I 
in which
R1 and R2 independently of one another are hydrogen,
C1xe2x80x94C20-alkyl, C3xe2x80x94C10-cycloalkyl or C3xe2x80x94C10-cycloalkenyl,
and as constituents
B) an effective amount of at least one compound chosen from the group consisting of
Ba) dibenzoylmethane compounds of the formula III 
in which
R3 is C1xe2x80x94C12-alkyl and
R4 is hydrogen, C1xe2x80x94C12-alkyl or C1xe2x80x94C12-alkoxy,
Bb) triazine derivatives of the formula IV 
in which
R5 to R7 independently of one another are optionally substituted C1xe2x80x94C20-alkyl, C5xe2x80x94C10-aryl, C5xe2x80x94C10-heteroaryl or
SpSil, where Sp is a spacer and Sil is a silane, oligosilane or polysiloxane radical,
X is the divalent radical 
where
R8 is hydrogen or optionally substituted C1xe2x80x94C20-alkyl, C5xe2x80x94C10-aryl or C5xe2x80x94C10-heteroaryl,
Bc) triazine derivatives of the formula V 
in which at least one o-hydroxyl group and at least one p-alkoxy group having 1 to 20 carbon atoms are bonded to the phenyl rings, .
Bd) the benzotriazole derivative of the formula VI 
Be) the benzimidazole derivative of the formula VII 
Bf) the benzotriazole derivative of the formula VIII 
Bg) o,oxe2x80x2,p,pxe2x80x2-tetrahydroxybenzophenone of the formula IX 
Bh) an organosiloxane benzalmalonate of the formula Xa 
in which
V1xe2x80x2 is the group 
V1 is a methyl group or V1xe2x80x2, or of the formula Xb 
in which V2xe2x80x2 is the group of the structure 
V2 is a methyl group or V2xe2x80x2
or mixtures of compounds of the formulae Xa and Xb,
where t is a value up to 100 and u is a value up to 20, with the proviso that u=0 when V1=V1xe2x80x2 and/or V2=V2xe2x80x2, and u is a value from 1 to 20 when V1=CH3 and/or V2=CH3,
optionally together with further compounds which absorb in the UV-A and UV-B region and which are known per se for cosmetic and pharmaceutical preparations, as sunscreens, where the UV-A-absorbing compounds are generally used in a lesser amount than the UV-B-absorbing compounds.
The sunscreen-containing cosmetic and pharmaceutical preparations are, as a rule, based on a carrier which comprises at least one oil phase. However, preparations based solely on water are also possible if compounds having hydrophilic substituents are used.
Accordingly, oils, oil-in-water and water-in-oil emulsions, creams and pastes, protective lipstick compositions or fat-free gels are suitable.
Suitable emulsions are inter alia also O/W macroemulsions, O/W microemulsions or O/W/O emulsions containing 4,4xe2x80x2-diarylbutadienes of the formula I in dispersed form, the emulsions being obtainable by phase inversion technology, as in DE-A-197 26 121.
Conventional cosmetic auxiliaries which may be suitable as additives are, for example, coemulsifiers, fats and waxes, stabilizers, thickeners, biogenic active substances, film formers, fragrances, dyes, pearlizing agents, preservatives, pigments, electrolytes (e.g. magnesium sulfate) and pH regulators. Suitable and preferred coemulsifiers are known W/O and also O/W emulsifiers such as polyglycerol esters, sorbitan esters or partially esterified glycerides. Typical examples of fats are glycerides; waxes which may be mentioned are, inter alia, beeswax, paraffin wax or microwaxes, possibly combined with hydrophilic waxes. Stabilizers which can be employed are metal salts of fatty acids such as, for example, magnesium, aluminum and/or zinc stearate. Examples of suitable thickeners are crosslinked polyacrylic acids and derivatives thereof: polysaccharides, in particular xanthan gum, guar guar, agar agar, alginates and tyloses, carboxymethylcellulose and hydroxyethylcellulose, also fatty alcohols, monoglycerides and fatty acids, polyacrylates, polyvinyl alcohol and polyvinylpyrrolidone. Examples of biogenic active substances are plant extracts, protein hydrolysates and vitamin complexes. Examples of customary film formers are hydrocolloids such as chitosan, microcrystalline chitosan or quaternized chitosan, polyvinylpyrrolidone, vinylpyrrolidone/vinyl acetate copolymers, polymers of the acrylic acid series, quaternary cellulose derivatives and similar compounds. Examples of suitable preservatives are formaldehyde solution, p-hydroxybenzoate or sorbic acid. Examples of suitable pearlizing agents are glycol distearic esters such as ethylene glycol distearate, but also fatty acids and fatty acid monoglycol esters. Dyes which can be used are the substances suitable and approved for cosmetic purposes, as listed, for example, in the publication xe2x80x9cKosmetische Fxc3xa4rbemittelxe2x80x9d [Cosmetic Colorants] from the Farbstoffkommission der Deutschen Forschungsgemeinschaft [Dyes Commission of the German Research Society], published by Verlag Chemie, Weinheim, 1984. These dyes are normally employed in a concentration of from 0.001 to 0.1%, based on the total weight of the mixture.
An additional content of antioxidants is generally preferred. Thus, it is possible to use as favorable antioxidants all antioxidants which are customary or suitable for cosmetic and/or dermatological applications.
The antioxidants are advantageously chosen from the group consisting of amino acids (e.g. glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazoles (e.g. urocanic acid) and derivatives thereof, peptides such as D,L-carnosine, D-carnosine, L-carnosine and derivatives thereof (e.g. anserine), carotenoids, carotenes (e.g. xcex2-carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, lipoic acid and derivatives thereof (e.g. dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (e.g thiorodoxin, glutathione, cysteine, cystine, cystamine and the glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl, and lauryl, palmitoyl, oleyl, xcex3-linoleyl, cholesteryl and glyceryl esters thereof) and salts thereof, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts), and sulfoximine compounds (e.g. buthionine sulfoximines, homocysteine sulfoximines, buthionine sulfones, penta-, hexa-, heptathionine sulfoximine) in very low tolerated doses (e.g. pmol to xcexcmol/kg), and also (metal) chelating agents (e.g. xcex1-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), xcex1-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA and derivatives thereof, unsaturated fatty acids and derivatives thereof (e.g. xcex3-linolenic acid, linoleic acid, oleic acid), folic acid and derivatives thereof, ubiquinone and ubiquinol and derivatives thereof, vitamin C and derivatives thereof (e.g. ascorbyl palpitate, Mg ascorbylphosphate, ascorbylacetate), tocopherol and derivatives (e.g. vitamin E acetate, tocotrienol), vitamin A and derivatives (vitamin A palmitate), and coniferyl benzoate of benzoin resin, rutinic acid and derivatives thereof, xcex1-glycosylrutin, ferulic acid, furfurylideneglucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiacic acid, nordihydroguaiaretic acid, trihydroxybutyrophenone, uric acid and derivatives thereof, mannose and derivatives thereof, zinc and derivatives thereof (e.g. ZnO, ZnSO4), selenium and derivatives thereof (e.g. selenomethionine), stilbenes and derivatives thereof (e.g. stilbene oxide, trans-stilbene oxide).
The amount of the abovementioned antioxidants (one or more compounds) in the preparations is preferably from 0.001 to 30% by weight, particularly preferably from 0.05 to 20% by weight, in particular from 1 to 10% by weight, based on the total weight of the preparation.
If vitamin E and/or derivatives thereof are used as the antioxidant(s), it is advantageous to choose their particular concentration from the range 0.001 to 10% by weight, based on the total weight of the formulation.
If vitamin A and/or derivatives thereof, or carotenoids are the antioxidant(s), it is advantageous to choose their particular concentration from the range 0.001 to 10% by weight, based on the total weight of the formulation.
Customary oil components in cosmetics are, for example, paraffin oil, glyceryl stearate, isopropyl mryristate, diisopropyl adipate, cetylstearyl 2-ethylhexanoate, hydrogenated polyisobutene, vaseline, caprylic/capric triglycerides, microcrystalline wax, lanolin and stearic acid.
The total amount of auxiliaries and additives can be from 1 to 80% by weight, preferably from 6 to 40% by weight, and the nonaqueous content (xe2x80x9cactive substancexe2x80x9d) can be from 20 to 80% by weight, preferably from 30 to 70% by weight, based on the compositions. The compositions can be prepared in a manner known per se, i.e. for example by hot, cold, hot-hot/cold or PIT emulsification. This is a purely mechanical process; no chemical reaction takes place.
Such sunscreen preparations can accordingly be in liquid, paste or solid form, for example as water-in-oil creams, oil-in-water creams and lotions, aerosol foam creams, gels, oils, marking pencils, powders, sprays or alcoholic-aqueous lotions.
Finally, it is also possible to co-use other substances which absorb in the UV region and are known per se provided they are stable in the overall system of the combination of UV filters to be used according to the invention.
Suitable UV filter substances which can be additionally used with the sunscreen combinations to be used according to the invention are any UV-A and UV-B filter substances. Examples which may be mentioned are:
The cosmetic and dermatological preparations according to the invention can advantageously further comprise inorganic pigments based on metal oxides and/or other metal compounds which are insoluble or virtually insoluble in water, in particular the oxides of titanium (TiO2), zinc (ZnO), iron (e.g. Fe2O3), zirconium (ZrO2), silicon (SiO2), manganese (e.g. MnO), aluminum (Al2O3), cerium (e.g. Ce2O3), mixed oxides of the corresponding metals, and admixtures of such oxides. Particular preference is given to pigments based on TiO2 and ZnO.
For the purposes of the present invention, it is particularly advantageous, but not obligatory, for the inorganic pigments to be present in hydrophobic form, i.e. to have been surface-treated to repel water. This surface treatment can involve providing the pigments with a thin hydrophobic layer in a manner known per se, as described in DE-A-33 14 742.
To protect human hair against UV rays, the suncreen combinations to be used according to the invention can be incorporated into shampoos, lotions, gels, hairsprays, aerosol foam creams or emulsions in concentrations of from 0.1 to 10% by weight, preferably from 1 to 7% by weight. The respective formulations can be used, inter alia, for washing, coloring and for styling the hair.
The sunscreen combinations to be used according to the invention are readily soluble in cosmetic oils and can be easily incorporated into cosmetic formulations. The emulsions prepared with the novel sunscreen combinations are notable in particular for their high stability, the sunscreen combinations themselves for their high photostability, and the preparations prepared with the sunscreen combinations for their pleasant feel on the skin.
The UV filter action of the sunscreen combinations to be used according to the invention can also be utilized for stabilizing active ingredients and auxiliaries in cosmetic and pharmaceutical formulations.
The examples below illustrate the use of the novel sunscreen combinations in more detail.